Coadministration has not been studied but is expected to decrease dolutegravir exposure due to induction of UGT1A1 and CYP3A by St John's wort. Interaction studies with dolutegravir and rifampicin (a strong inducer) showed that the effect of induction on dolutegravir concentrations can be overcome by administering an additional 50 mg dose of dolutegravir. The US Prescribing Information for dolutegravir advises to avoid coadministration with St John's wort due to insufficient data to make dosing recommendations. However, the European SPC recommends that dolutegravir be dosed at 50 mg twice daily, but that alternative combinations should be used where possible in INSTI-resistant patients. This dose adjustment should be maintained for approximately 2 weeks after stopping St John’s wort as the inducing effect may persist after discontinuation of a strong inducer. A recent study suggests a low risk of a clinically relevant pharmacokinetic interaction with low-hyperforin formulations (<1 mg/day) of St John’s Wort (hyperforin is the constituent responsible for induction of CYPs and P-gp).